Muscle relaxants depolarizing

Depolarizing muscle relaxants act as agonists (excitatory) of the NM nicotine receptor on the motor endplate. The interaction with the receptor leads to a long-lasting depolarization of the motor endplate. Acetylcholine can no longer excite because the receptor channel is already open.

Depolarizing muscle relaxants such as suxamethonium (succinylcholine), in contrast to acetylcholine, are not degraded by acetylcholinesterase. In this respect, the NM - nicotinic receptor channel is opened for a long time and the motor end plate remains depolarized for a long time. This state of depolarization is called depolarization block, or phase I block.

The "multicentric" activation of the muscle fibers initially results in a brief contraction of the muscles. This can be observed in the patient as fasciculation of the muscles (uncoordinated muscle tremor). The exception to this is the eye muscles which may respond with a sustained contraction.

The persistent depolarization prevents renewed excitation by acetylcholine. This phase of uncoordinated fasciculation passes into aflaccid paralysis phase. The muscle is unexcitable. The effect cannot be reversed by other drugs (antagonizable).

If phase I block persists for a long time, e.g. by repeated administration of suxamethonium, a phase II block (depolarization block) may follow. This state can be partially reversed by cholinesterase inhibitors. This state is probably due to a kind of desensitization of the_{NM nicotine receptors}(receptor phosphorylation).

The only active substance approved for use in humans is succinylcholine (suxamethonium), which is easy to control because it is short-acting. Apart from minor and rare side effects, preferred muscle relaxants have a rapid onset of action and a short duration of action in the sense of good controllability of their action. All nondepolarising muscle relaxants (NDMR) can release histamine to varying degrees. Anaphylactic reactions are possible. Allergic reactions are described. Regarding potential side effects, "synthetic receptors" with high binding affinity to succinylcholine seem to be an option (Zhang X et al. 2019).

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4. Zhang X et al (2019) Supramolecular therapeutics to treat the side effects induced by a depolarizing neuromuscular blocking agent. Theranostics 9:3107-3121.